Insulin Sensitivity and Liver Fat: Role of Iron Load

Context: Increased liver fat (LF) is associated with insulin resistance. However, a considerable individual variability between LF and insulin sensitivity (IS) is observed, and at equal levels of LF, insulin-resistant as well as insulin-sensitive individuals are found. Objective: Our objective was to study whether hepatic iron load (HIL) explains some of the variation between IS and LF. Design: HIL was measured using a quantitative T2* magnetic resonance gradient echo imaging technique, and LF was measured by (1)H-magnetic resonance spectroscopy. Low T2* values indicate high HIL. We studied the association of LF and HIL with anthropometric data and IS. A total of 113 healthy nondiabetic subjects [69 females, 44 males; age 47 +/- 1 yr; body mass index (BMI) = 28.9 +/- 0.5 kg/m(2)] at increased risk for type 2 diabetes were included in the study. Results: T2* values adjusted for age negatively associated with serum ferritin levels (P < 0.0001) and positively associated with IS (P = 0.009). In addition, T2* values associated with LF (P = 0.008) but not with BMI (P = 0.6). In a multivariate model, IS adjusted for gender, age, and BMI was associated with T2* values (P = 0.015). IS adjusted for gender and age was independently associated with LF (P = 0.033) and T2* values (P = 0.004). In a stepwise regression analysis, LF explained 13.5% (P < 0.01) of the variation in IS, and HIL explained an additional 4.1% (P = 0.03). Conclusions: HIL explains part of the variation between LF and IS. The mechanism by which iron load induces insulin resistance is possibly independent of the pathways involved in insulin resistance induced by fatty liver disease. (J Clin Endocrinol Metab 96: E958-E961, 2011)